1. Field of the Invention
The present invention relates to a device for depletion of leukocytes or white blood cells from leukocyte-containing fluids, especially blood products having a low viscosity, such as whole blood or platelet derivatives, in which a leukocyte removal filter can maintain leukocyte depletion at a high level. The present invention further relates to a method for preparing leukocyte-depleted products using the device.
2. Description of the Related Art
Recent studies on immunology and blood transfusion reveal that adverse post-transfusion reactions are provoked by leukocytes present in blood products. In order to prevent, among others, relatively moderate headache, vomiting, chill, nonhemolytic febrile transfusion reactions, etc., it is recognized necessary to reduce the white cell count infused into a recipient by single transfusion to approximately 10.sup.8 or less. To satisfy the desired white cell count, leukocytes should be removed until the residual leukocytes decrease to the level of less than 10.sup.-1 to 10.sup.-2.
With regard to graft-versus-host-reactions (GVHR), cytomegalovirus infections and alloimmunization which are severe side effects, it is expected that these adverse effects could be prevented by removing leukocytes until the residual leukocytes become less than 10.sup.-4 to 10.sup.-6.
For these reasons, it is therefore general in blood products to remove leukocytes using a leukocyte removal filter comprising non-woven cloth or porous materials.
A leukocyte removal filter is often employed by mounting the filter to a device for leukocyte depletion, which is equipped with a conduit for connecting the filter and flowing blood therethrough. In general, such a device has an inlet port and an outlet port at the upstream and downstream sides of the leukocyte removal filter, respectively, which ports are connected to the conduit. Such a device for leukocyte depletion equipped with a leukocyte removal filter is employed for direct transfusion to a patient, i.e., putting the device at a patient's bedside, or employed for preparing leukocyte-depleted products at blood centers.
For minimizing a load on patients, leukocyte depletion at a bedside is operated usually by controlling a blood flow rate to a level of approximately 5 to 10 ml/min. On the other hand, a method for leukocyte depletion performed at blood centers or elsewhere to prepare leukocyte-depleted products comprises connecting a device for leukocyte depletion having a leukocyte removal filter mounted thereto to a blood collection bag, in which blood to be treated is put, passing the blood through the filter to remove leukocytes, and recovering leukocyte-depleted products in a transfer bag (bag--bag filtration). Therefore, a distance (head) from the blood collection bag to the transfer bag is generally adjusted to 0.5 to 1.5 meter so that leukocytes are removed by gravity drop.
Where blood products are those having a low viscosity like platelet concentrates, such bag--bag filtration frequently results in an average blood flow rate exceeding 70 ml/min in a conventional device for leukocyte depletion so that leukocytes adhere to a filtering material only with difficulty to reduce its efficiency of leukocyte depletion. It was thus difficult to stably maintain the residual rate of leukocytes to 10.sup.-4 or less.
On the other hand, when too slow an average blood flow rate encounters problems that it takes too much time to prepare leukocyte-depleted products and it is difficult to process a large volume of blood products. Too slow a flow rate in biological products such as blood products means that a contact time of a filtering material with blood cells is prolonged, resulting in the formation of microaggregates due to activation of blood cells and thus leading to reduction in quality of the resulting leukocyte-depleted products. Furthermore, in the case that platelets are recovered as effective components, there is a problem that highly viscous platelets might be adhered to a filtering material to lower the recovery rate of platelets. An additional concern arises that many leukocytes might be adhered to the upper layer of a leukocyte removal filter to cause clotting of the filter with leukocytes so that pores of the filtering material are occluded and the filtering material at the lower layer of the occluded portion might loose the ability of effectively removing leukocytes. Such clotting caused by leukocytes might greatly decrease a blood flow rate or even prevent blood from flowing down.
JP-U-1-117348 discloses a transfusion set having a narrow portion for controlling flow rate which is employed for transfusion of a drug substantially free of solid, such as glucose solution or Ringer's solution. However, this transfusion set is not designed for treating a leukocyte-containing suspension comprising blood cells and viscous plasma components. JP-U-1-117348 does not even suggest any application to a flow rate controlling mechanism for removing leukocytes.
Some devices for leukocyte depletion used at a bedside may have a roller clamp above or beneath a leukocyte removal filter. The roller clamp provided for suitably controlling a transfusion rate applied to patients is a means for gradually adjusting a desired flow rate, while measuring the drop count and blood weight. Accordingly, where a large volume of leukocyte-depleted products are prepared, there arise problems that it takes long and the position of a roller at the roller clamp may change due to a passage resistance of blood during the filtration of blood and hence, a flow rate is liable to change.
In a device for depletion of leukocytes it is also known to control a blood flow rate by decreasing a head. However, according to this method for decreasing a head, the distance between an inlet port and a leukocyte removal filter becomes inevitably short so that difficulties occur in preventing the air from permeating into the filter and in mounting a chamber for removing gels in the device for leukocyte depletion. Furthermore, where the head is too small, filtration must be conducted in some occasion by putting the leukocyte removal filter on the floor or giving a tilt to the filter. In this case, problems encounter that the ability of leukocyte depletion might be reduced due to blood flowing only on one side or a bag might be exchanged only with difficulty.